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Dianna K. Wheaton, Yuquan Wen, Kirsten G. Locke, Martin Klein, Sara J. Bowne, Lori S. Sullivan, Joseph W. Ray, Stephen P. Daiger, David G. Birch; Phenotypic Characterization Of Three Families With Autosomal Dominant Retinitis Pigmentosa (adRP) Due To Mutations In KLHL7. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5402.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the phenotype caused by mutations in the BTB-Kelch protein, KLHL7, responsible for RP42 autosomal dominant retinitis pigmentosa (adRP). Disease-causing mutations in KLHL7 have recently been described (Friedman et al, Am J Hum Gen, 2009) and the phenotype associated with the initial missense mutation, c.449G>A characterized (Hugosson et al, Arch Ophthal, 2010). Reported herein is a phenotypic assessment of 3 unrelated families (RFS038, RFS061, RFS073) each bearing different KLHL7 missense mutations (c.458C>T, c.457G>A, c.449G>A, respectively).
Each family had an established inheritance pattern of adRP. In family RFS038, 3 affected individuals (ascertainment age=45, 50, 76y; males) were available for exam, whereas families RFS061 (35y; male) & RFS073 (59y; female) only the probands were available. Vision testing included acuity (VA), static (Humphrey) and kinetic (Goldmann) visual fields, dark adaptometry (DA), full-field electroretinography (ffERG), frequency-domain optical coherence tomography (fdOCT), and fundus photography. Longitudinal vision data was available from each family.
Visual field loss and night blindness were the major reasons for presentation. Best-corrected VA was relatively preserved (≤20/50; better eye) thru age 60 (4/5 patients). Static and kinetic fields showed concentric constriction to central 10-20º by age 60; 2 patients with Goldmann fields also exhibited bilateral field retention in the far periphery (65-80º & 70-90º temporally). All 5 patients had elevated DA threshold at initial visit (2.9 - 6.1 log units), diminished rod (0-9 µV) and cone (0.1-22 µV) ffERG amplitudes, and delayed implicit times. fdOCT showed retention of foveal structure and integrity (observable IS/OS junction) thru age 60; 1 patient had cystoid macular edema. Fundus imaging showed classic signs of RP (e.g., bone-spicule, vessel attenuation, waxy disc pallor). Similar clinical phenotypes were shared by patients bearing the 3 different disease-causing mutations.
Mutations in KLHL7 cause a late-onset form of dominant retinal degeneration that preferentially affects rod photoreceptors. A pattern of retained foveal function and bilateral concentric constriction of the visual field with far periphery sparing was observed; consistent with the previous phenotypic report. ffERG findings were characteristic of those observed in other forms of adRP.
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